LRP-1 and human pleural mesothelial cells

http://www.ncbi.nlm.nih.gov/pubmed/21885677

Am J Respir Cell Mol Biol. 2011 Sep 1. [Epub ahead of print]
LRP-1 Regulates Collagen 1 Expression, Proteolysis, and Migration in Human Pleural Mesothelial Cells.
Tucker TA, Williams L, Koenig K, Kothari H, Komissarov AA, Florova G, Mazar AP, Allen TC, Bdeir K, Rao LV, Idell S.
Source
Texas Lung Injury Institute, University of Texas Health Science Center at Tyler, 11937 US Higway 271, Tyler, Texas, 75708, United States.

Abstract
The low-density lipoprotein receptor-related protein 1 (LRP-1) binds and can internalize a diverse group of ligands including members of the fibrinolytic pathway; urokinase plasminogen activator (uPA) and its receptor, uPAR. In this study, we characterized the role of LRP-1 in uPAR processing, collagen synthesis, proteolysis and migration in pleural mesothelial cells (PMCs). When PMCs were treated with the pro-inflammatory cytokines TNF-α and IL-1β, LRP-1 significantly decreased at both the mRNA and protein levels (70% and 90% respectively, p<0.05). Consequently, uPA-mediated uPAR internalization was reduced by 80% in the presence of TNF-α or IL-1β (p<0.05). In parallel studies, LRP-1 neutralization with receptor associated protein; RAP, significantly reduced uPA-dependent uPAR internalization and increased uPAR stability in PMCs. LRP-1 deficient cells demonstrated increased uPAR t1/2 versus LRP-1 expressing PMCs. uPA enzymatic activity was also increased in LRP-1 deficient and neutralized cells and RAP potentiated uPA-dependent migration in PMCs. Collagen expression in PMCs was also induced by uPA and the effect was potentiated in RAP-treated cells. These studies indicate that TNF-α and IL-1β regulate LRP-1 in PMCs and that LRP-1 thereby contributes to a range of pathophysiologically relevant responses of these cells.